Dehydroandrographolide (Deh) from Andrographis paniculata (Burm.f.) Wall has strong anti-inflammatory and antioxidant activities. To explore the role of Deh in acute lung injury (ALI) of coronavirus disease 19 (COVID-19) and its inflammatory molecular mechanism. Liposaccharide (LPS) was injected into a C57BL/6 mouse model of ALI, and LPS + adenosine triphosphate (ATP) was used to stimulate BMDMs in an in vitro model of ALI. In an in vivo and in vitro model of ALI, Deh considerably reduced inflammation and oxidative stress by inhibiting NLRP3-mediated pyroptosis and attenuated mitochondrial damage to suppress NLRP3-mediated pyroptosis through the suppression of ROS production by inhibiting the Akt/Nrf2 pathway. Deh inhibited the interaction between Akt at T308 and PDPK1 at S549 to promote Akt protein phosphorylation. Deh directly targeted PDPK1 protein and accelerated PDPK1 ubiquitination. 91-GLY, 111-LYS, 126-TYR, 162-ALA, 205-ASP and 223-ASP may be the reason for the interaction between PDPK1 and Deh. Deh from Andrographis paniculata (Burm.f.) Wall presented NLRP3-mediated pyroptosis in a model of ALI through ROS-induced mitochondrial damage through inhibition of the Akt/Nrf2 pathway by PDPK1 ubiquitination. Therefore, it can be concluded that Deh may be a potential therapeutic drug for the treatment of ALI in COVID-19 or other respiratory diseases.

Objective: Omicron has become a dominant variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide. A majority of individuals infected with Omicron SARS-CoV-2 experience no or mild symptoms, but exhibit excessively higher transmissibility than those infected with the ancestral variant in 2020. This study aimed to identify the distinctive clinical types and laboratory markers of coronavirus disease 2019 (COVID-19). Methods: This retrospective study was performed in multiple medical centers that treated patients infected with COVID-19. Demographic characteristics and laboratory data, such as the viral shedding time, blood routine test results, and biochemical indicators, were initially recorded after admission. Results: A total of 59 patients with ancestral SARS-CoV-2 infection and 112 patients with Omicron SARS-CoV-2 infection were eventually included. Patients with Omicron SARS-CoV-2 infection were asymptomatic, whereas the ancestral variant was a common type. Patients with Omicron SARS-CoV-2 infection had markedly higher white blood cell (WBC), eosinophil, and platelet (PLT) counts, but remarkably lower lymphocyte counts. The concentration of D-dimer was lower in the Omicron group than in the ancestral variant group. The Omicron variant showed a notably shorter viral shedding time than the ancestral variant, with median durations of 11 and 16 days, respectively ( p < 0.001). Multivariate analysis revealed that WBC count, lymphocyte count, eosinopenia, D-dimer, alanine transaminase (ALT), and viral shedding time were independent risk factors for predicting Omicron SARS-CoV-2 infection. The receiver operating characteristic (ROC) curves showed that viral shedding time, ALT, D-dimer, and lymphocyte count favored differential diagnosis of ancestral SARS-CoV-2 infection, whereas WBC and eosinophil counts favored differential diagnosis of Omicron SARS-CoV-2 infection. Conclusions: A majority of patients with Omicron SARS-CoV-2 infection are asymptomatic. WBC count, eosinopenia, and viral shedding time were identified as independent factors for predicting the risk of Omicron SARS-CoV-2 infection. Viral shedding time and eosinophil count were identified as biomarkers for differential diagnosis of ancestral and Omicron SARS-CoV-2 infections, respectively. Clinical features and various laboratory tests may serve as auxiliary reference indicators to complement viral nucleic acid testing (the diagnostic gold standard) for preliminary stratification of suspected COVID-19 cases, particularly in retrospective analysis of variant-related characteristics.